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Changes in bone mineral metabolism in patients with recurrent urolithiasis and vitamin D receptor gene polymorphisms. Preliminary results
Alteraciones en el metabolismo mineral óseo en pacientes con urolitiasis de repetición y polimorfismos del gen del receptor de la vitamina D. Resultados preliminares.
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Mª Jesús Moyano Franco, Mª Jesús Gómez de Tejada Romero, Raúl García Lozano, Rosa Moruno, Rosa Ortega, Vicente Martí, Rocío Sánchez Palen
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SUMMARY Bone health, within calcium kidney stone disease is a matter of controversy. On the other hand, some genetic studies have shown an association between some Vitamin D receptor polymorphisms and calcium kidney stone disease. Main objective: To study the possible association between calcium kidney stone disease with bone metabolism and some Vitamin D receptor polymorphisms. Patients and Methods: This is a case-control study, with seventy-two subjects of both genders divided into two groups: Group I: cases, composed by 51 patients suffering from calcium kidney stone disease. Twenty-four of them had no hypercalciuria, 16 had absortive hypercalciuria and 11 had renal hypercalciuria. Group II: controls, composed by 21 people, without either urolithiasis or hypercalciuria. We performed a complete study including biochemical markers of bone mineral remodelling, bone mineral density (BMD) was estimated both in the lumbar spine (L2-L4) and femoral neck, and also VDR polymorphism for the loci b, a and t. Results: Patients with urolithiasis had lower values of BMD both in the lumbar spine and femoral neck, compared to controls. Z-score were lower in the lumbar spine and femoral neck (p =0,045 y 0,031, respectively). Those patients with absorptive hypercalciuria had higher BMD in the femoral neck than those with renal hypercalciuria and non-hypercalciuria. Because they had more weight and height all the statistical study was performed alter adjusting by these two variables and statistical significance was then only stated between patients with hypercalciuria and without it. Patients with urolithiasis had higher values of 1,25 (OH)2 vitamin D (p=0,002), and lower of PTH (p=0,049), without any relationship to hypercalciuria and its subtypes. Seventy six percent of the patients had a daily calcium intake lower than 800 mg/day. The distribution of VDR alleles in patients with urolithiasis was similar to controls, although after grouping genotypes, a lower distribution of BB and tt polymorphisms were observed in patients suffering from urolithiasis. Conclusions: Calcium kidney stone disease by itself produces a decrease in BMD, more intense in femoral neck, independently the presence or absence of hypercalciuria. Patients suffering from urolitihiasis have higher values of 1,25 (OH)2 vitamin D than non-hypercalciuric patients and lower values of PTH probably due to a low dietary calcium intake. In our population studied there is no relationship between VDR polymorphisms and the presence of calcium kidney stone disease. Because the reduced number of patients of our study, more studies are needed to obtain definitely conclusions.
Keywords:
Key words: Calcium kidney stone disease
Absortive hypercalciuria
Renal hypercalciuria
Bone mineral density
Calcium intake
Vitamin D polymorphism
Existe controversia sobre la afectación ósea en la litiasis renal cálcica. Por otro lado, algunos estudios genéticos han encontrado asociación entre los polimorfismos del receptor de la vitamina D (VDR) y la urolitiasis. Objetivo principal: Relacionar la nefrolitiasis cálcica de repetición con el metabolismo óseo y los polimorfismos del gen del VDR. Material y métodos: Estudio de casos y controles, estando el grupo de casos formado por 51 pacientes con litiasis renal de repetición, que subdividimos en no hipercalciúricos (NHC, n = 27), hipercalciúricos absortivos (HCA, n = 10) e hipercalciúricos renales (HCR, n = 14); el grupo control, formado por 21 sujetos sin historia de litiasis renal ni hipercalciuria. Se les determinaron parámetros del metabolismo fosfo-cálcico, marcadores de remodelado óseo, densidad mineral ósea (DMO) en columna lumbar y en cuello femoral, y polimorfismos del gen del VDR para los loci b, a y t. Resultados: Los pacientes litiásicos presentaron frente a los controles una DMO inferior tanto en L2-L4 como en cuello femoral (Z-score, p = 0,045 y 0,031), niveles superiores de 1,25 (OH)2 vitamina D (p = 0,002) e inferiores de PTH (p = 0,049), y una menor ingesta cálcica (p < 0,001). Los HCA mostraron una mayor DMO frente a los NHC (sólo significativo en cuello femoral). Los pacientes con LRC no mostraron diferencias en las frecuencias genotípicas estudiadas frente a los controles. Al reagrupar los alelos, sólo se apreció una menor frecuencia del genotipo BB respecto al Bb-bb, y del tt frente al TT-Tt, en los pacientes litiásicos (p = 0,098 y p = 0,051, respectivamente). Conclusiones: La litiasis renal cálcica parece influir en la DMO de cuello femoral. Los pacientes litiásicos mostraron niveles elevados de 1,25 (OH)2 vitamina D, posiblemente relacionado con la baja dieta cálcica. Los genotipos homocigóticos BB y tt parecen ser menos frecuentes entre los pacientes con litiasis renal cálcica.
Palabras clave:
Palabras clave: Litiasis renal cálcica, hipercalciuria absortiva, hipercalciuria renal, densidad mineral ósea, polimorfismos del receptor de la vitami
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